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Efficacy of antineoplastic treatment is associated with the use of antibiotics
that modulate intestinal microbiota
#MMPMID27471619
Pflug N
; Kluth S
; Vehreschild JJ
; Bahlo J
; Tacke D
; Biehl L
; Eichhorst B
; Fischer K
; Cramer P
; Fink AM
; von Bergwelt-Baildon M
; Stilgenbauer S
; Hallek M
; Cornely OA
; Vehreschild MJ
Oncoimmunology
2016[Jun]; 5
(6
): e1150399
PMID27471619
show ga
Reduced anticancer efficacy of cyclophosphamide and platinum salts has been
reported in animals treated with anti-Gram-positive antibiotics. These effects
were related to translocation of Gram-positive bacteria during mucositis with
subsequent induction of cytotoxic oxygen reactive species and tumor invasion by
pathogenic Th17 cells. To assess these hypotheses in a clinical setting, we
identified patients receiving cyclophosphamide for chronic lymphocytic leukemia
(CLL) and cisplatin for relapsed lymphoma. Data originated from the CLL8 trial
(NCT00281918) and the Cologne Cohort of Neutropenic Patients (NCT01821456).
Relevant antibiotics were defined as compounds with primary activity against
Gram-positive bacteria. We evaluated their impact on response, progression-free
survival (PFS) and overall survival (OS) by Kaplan-Meier methodology and Cox
proportional hazards regression analysis. Among 800 available CLL patients, those
receiving anti-Gram-positive antibiotics (n = 45/800) achieved a significantly
lower overall response rate (OR 74.3% vs. 90.2%, p = 0.007). Patients with
anti-Gram-positive antibiotics progressed significantly earlier, had a reduced OS
(median PFS 14.1 vs. 44.1 mo, p < 0.001; median OS 56.1 vs. 91.7 mo, p < 0.001)
and multivariate analysis showed that administration of anti-Gram-positive
antibiotic treatment was independently associated with reduced PFS (Hazard ratio
(HR) 2.090, p = 0.001) and OS (HR 2.966, p < 0.001). Of 122 patients with
relapsed lymphoma, those treated with anti-Gram-positive antibiotics (n = 21/122)
achieved a significantly lower OR rate (70.3% vs. 42.9%, p = 0.016). Patients
with anti-Gram-positive antibiotics progressed significantly earlier than others
(median PFS 2.3 vs. 11.5 mo, p = 0.001). As for multivariate analysis, the use of
anti-Gram-positive antibiotics was independently associated with reduced PFS (HR
2.237, p = 0.012) and OS (HR 7.831, p < 0.001). Our data supports a potential
negative impact of anti-Gram-positive antibiotics on the anticancer activity of
cyclophosphamide and cisplatin in a clinical setting.
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